Phenocopying Glioblastoma: A Review

Oraiopoulou, Mariam-Eleni; Tzamali, Eleftheria; Papamatheakis, Joseph; Sakkalis, Vangelis

doi:10.1109/rbme.2021.3111744

Cited by 9 publications

(6 citation statements)

References 170 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on our findings (Supplementary Fig. S2C and Supplemen structures [13,31]. VM tubular structures can often be formed by one layer of cancer cells that may or may not be a functional tubule and this process is cell line-specific [32].…”

Section: Discussionmentioning

confidence: 58%

The in vitro dynamics of pseudo-vascular network formation

Oraiopoulou,

Couturier,

Bunce

et al. 2024

Br J Cancer

Self Cite

View full text Add to dashboard Cite

Background/Objectives Pseudo-vascular network formation in vitro is considered a key characteristic of vasculogenic mimicry. While many cancer cell lines form pseudo-vascular networks, little is known about the spatiotemporal dynamics of these formations. Methods Here, we present a framework for monitoring and characterising the dynamic formation and dissolution of pseudo-vascular networks in vitro. The framework combines time-resolved optical microscopy with open-source image analysis for network feature extraction and statistical modelling. The framework is demonstrated by comparing diverse cancer cell lines associated with vasculogenic mimicry, then in detecting response to drug compounds proposed to affect formation of vasculogenic mimics. Dynamic datasets collected were analysed morphometrically and a descriptive statistical analysis model was developed in order to measure stability and dissimilarity characteristics of the pseudo-vascular networks formed. Results Melanoma cells formed the most stable pseudo-vascular networks and were selected to evaluate the response of their pseudo-vascular networks to treatment with axitinib, brucine and tivantinib. Tivantinib has been found to inhibit the formation of the pseudo-vascular networks more effectively, even in dose an order of magnitude less than the two other agents. Conclusions Our framework is shown to enable quantitative analysis of both the capacity for network formation, linked vasculogenic mimicry, as well as dynamic responses to treatment.

show abstract

Section: Discussionmentioning

confidence: 58%

The in vitro dynamics of pseudo-vascular network formation

Oraiopoulou,

Couturier,

Bunce

et al. 2024

Br J Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…We have demonstrated potential for dynamic imaging to inform on the diversity of VM-competence between cancer cells that form pseudo-vascular networks in vitro , however, there remain several limitations to our approach that should be addressed in future. First, cancer cells form tubes in the xy plane of the BME-coated wells used here and fail to form 3D structures [13, 33]. VM tubular structures are often formed by one layer of cancer cells that may or may not be a functional tubule and this process is cell line-specific [34].…”

Section: Discussionmentioning

confidence: 99%

Thein vitrodynamics of pseudo-vascular network formation

Oraiopoulou,

Couturier,

Bunce

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Pseudo-vascular network formation capacityin vitrois considered a key characteristic of vasculogenic mimicry. While many cancer cell lines are known to form pseudo-vascular networks, little is known about the spatiotemporal dynamics of these formations. Here, we present a framework for monitoring and characterising the dynamic formation and dissolution of pseudo-vascular networksin vitro. The framework combines time-resolved optical microscopy with open-source image analysis for network feature extraction and statistical modelling. The framework is demonstrated by comparing diverse cancer cell lines associated with vasculogenic mimicry, then in detecting response to drug compounds proposed to affect formation of vasculogenic mimics. Dynamic datasets collected were analysed morphometrically and a descriptive statistical analysis model was developed in order to measure stability and dissimilarity characteristics of the pseudo-vascular networks formed. Melanoma cells formed the most stable pseudo-vascular networks and were selected to evaluate the response of their pseudo-vascular networks to treatment with axitinib, brucine and tivantinib. Our framework is shown to enable quantitative analysis of both the capacity for network formation, linked vasculogenic mimicry, as well as dynamic responses to treatment.

show abstract

“…There is also recent literature concerning the in vivo combination of the two drugs, yet in cancer types other than GB 24 – 26 . Although conventional 2D in vitro end-point drug-screening assays provide valuable information regarding drug effectiveness and potency, they have thus far proven insufficient to predict the spatiotemporal response of tumors 27 . On the other hand, animal studies, though closer to human, are most usually time-consuming and cost-ineffective, while they fail to adequately identify drug molecular and mechanistic interactions.…”

Section: Introductionmentioning

confidence: 99%

The Temozolomide–Doxorubicin paradox in Glioblastoma in vitro–in silico preclinical drug-screening

Oraiopoulou,

Tzamali,

Psycharakis

et al. 2024

Sci Rep

Self Cite

View full text Add to dashboard Cite

Adjuvant Temozolomide is considered the front-line Glioblastoma chemotherapeutic treatment; yet not all patients respond. Latest trends in clinical trials usually refer to Doxorubicin; yet it can lead to severe side-effects if administered in high doses. While Glioblastoma prognosis remains poor, little is known about the combination of the two chemotherapeutics. Patient-derived spheroids were generated and treated with a range of Temozolomide/Doxorubicin concentrations either as monotherapy or in combination. Optical microscopy was used to monitor the growth pattern and cell death. Based on the monotherapy experiments, we developed a probabilistic mathematical framework in order to describe the drug-induced effect at the single-cell level and simulate drug doses in combination assuming probabilistic independence. Doxorubicin was found to be effective in doses even four orders of magnitude less than Temozolomide in monotherapy. The combination therapy doses tested in vitro were able to lead to irreversible growth inhibition at doses where monotherapy resulted in relapse. In our simulations, we assumed both drugs are anti-mitotic; Temozolomide has a growth-arrest effect, while Doxorubicin is able to cumulatively cause necrosis. Interestingly, under no mechanistic synergy assumption, the in silico predictions underestimate the in vitro results. In silico models allow the exploration of a variety of potential underlying hypotheses. The simulated-biological discrepancy at certain doses indicates a supra-additive response when both drugs are combined. Our results suggest a Temozolomide–Doxorubicin dual chemotherapeutic scheme to both disable proliferation and increase cytotoxicity against Glioblastoma.

show abstract

Phenocopying Glioblastoma: A Review

Cited by 9 publications

References 170 publications

The in vitro dynamics of pseudo-vascular network formation

The in vitro dynamics of pseudo-vascular network formation

Thein vitrodynamics of pseudo-vascular network formation

The Temozolomide–Doxorubicin paradox in Glioblastoma in vitro–in silico preclinical drug-screening

Contact Info

Product

Resources

About